Jesus Ramirez-Bermudez M.D., Ph.D. , Miguel Restrepo-Martinez M.D. , Mariana Espinola-Nadurille M.D., M.P.H. , Victoria Martinez-Angeles M.D. , Juan Carlos Lopez-Hernandez M.D. , Laura E. Hernandez-Vanegas M.D. , Francisco Martinez-Carrillo M.D. , Ramiro Ruiz-Garcia M.D. , Veronica Rivas-Alonso M.D. , Jose Flores-Rivera M.D. , Thomas A. Pollak M.R.C.Psych., Ph.D.
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The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis.</span></p></div><div><h3>Methods</h3><p><span>This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and </span>Neurosurgery<span><span><span> of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of </span>creatine phosphokinase, and hyperthermia. A </span>logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions.</span></p></div><div><h3>Results</h3><p>A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics.</p></div><div><h3>Conclusions</h3><p><span>Our study supports previous observations about the high frequency of autonomic dysfunction<span>, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels </span></span>in patients<span> with anti-NMDAR encephalitis following the administration of antipsychotic medications. 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A </span>logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions.</span></p></div><div><h3>Results</h3><p>A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). 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引用次数: 0
摘要
背景:抗N-甲基-D-天冬氨酸受体脑炎(ANMDARE)是一种神经免疫性疾病,免疫治疗常能改善病情。在精神症状占主导地位的早期阶段,使用抗精神病药物进行对症治疗很常见,但这些药物的使用与包括神经性恶性综合征(NMS)在内的严重副作用有关。观察到对抗抑郁药的不良反应,引起对 NMS 的怀疑,已被列为可能患有自身免疫性精神病的一个标准:这项病例对照研究纳入了在转诊至墨西哥国家神经病学与神经外科研究所(National Institute of Neurology and Neurosurgery of Mexico)之前接受过抗精神病药物治疗并被诊断为明确患有 ANMDARE 的患者,以及在转诊之前未接受过抗精神病药物治疗的 ANMDARE 患者。两组患者均测量了神经系统和全身特征,这些特征用于衡量抗精神病药物不良反应,从而引起对 NMS 的怀疑,其中包括运动障碍、自主神经不稳定、全身僵硬、肌酸磷酸激酶浓度升高和高热。采用逻辑回归分析确定既往使用过抗精神病药物与 NMS 类反应发生之间的关系:研究共纳入了112名确诊的ANMDARE患者。其中 50 名患者在转诊至我院前曾接受过抗精神病药物治疗。在这组患者中,有 36 名患者(72%)最初被归类为出现不良反应,引起了对 NMS 的怀疑,其特征如下:运动障碍(64%)、自主神经不稳定(58%)、全身僵硬(52%)、肌酸磷酸激酶浓度升高(50%)和高热(14%)。六名患者符合 NMS 标准(12%)。与临床评估前未服用抗精神病药物的患者进行比较后发现,在运动失调、自律神经不稳定、全身僵硬、肌酸磷酸激酶浓度升高或高热的发生率方面,组间差异并不明显。在不同的抗精神病药物中,与未服用抗精神病药物的患者相比,只有氟哌啶醇与全身僵直有显著相关性:我们的研究证实了之前关于抗 NMDAR 脑炎患者在服用抗精神病药物后频繁出现自主神经功能紊乱、高热、心动过速、全身僵硬和 CPK 水平升高的观察结果。尽管如此,我们的研究并不表明非典型抗精神病药物与这些神经系统症状的出现之间存在因果关系,因为在未接受抗精神病药物治疗的患者群体中,这些症状也同样频繁出现。
Examining the Features of Neuroleptic Malignant Syndrome in Anti-NMDA Receptor Encephalitis: A Case-Control Study
Background
Anti–N-methyl-D-aspartate receptor encephalitis (ANMDARE) is a neuroimmunological disorder that frequently improves with immunotherapy. Symptomatic treatment with antipsychotics is common in the early stages when psychiatric symptoms predominate, and their use has been associated with serious side effects including neuroleptic malignant syndrome (NMS). The observation of an adverse response to antipsychotics, raising the suspicion of NMS, has been included as a criterion for possible autoimmune psychosis.
Methods
This case-control study included patients who received antipsychotics before referral to the National Institute of Neurology and Neurosurgery of Mexico, where they were diagnosed as having definite ANMDARE, and patients with ANMDARE who did not receive antipsychotics before referral. The neurologic and systemic features that are used to measure an adverse response to antipsychotics, raising the suspicion of NMS, were measured in both groups, including akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, and hyperthermia. A logistic regression analysis was used to determine the relationship between the previous use of antipsychotics and the occurrence of NMS-like reactions.
Results
A total sample of 112 patients with definite ANMDARE were included in the study. Fifty patients received antipsychotics before being referred to our institution. In this group, thirty-six patients (72%) were initially classified as having an adverse response, raising the suspicion of NMS, with the following features: akinesia (64%), autonomic instability (58%), generalized rigidity (52%), elevated concentrations of creatine phosphokinase (50%), and hyperthermia (14%). Six patients fulfilled the criteria for NMS (12%). The comparison with patients who did not receive antipsychotics before the clinical assessment did not show a significant difference between groups regarding the frequency of akinesia, autonomic instability, generalized rigidity, elevated concentrations of creatine phosphokinase, or hyperthermia. Among different antipsychotics, only haloperidol was significantly associated with generalized rigidity as compared to patients who did not receive antipsychotics.
Conclusions
Our study supports previous observations about the high frequency of autonomic dysfunction, hyperthermia, tachycardia, rigidity, and elevated creatine phosphokinase levels in patients with anti-NMDAR encephalitis following the administration of antipsychotic medications. Nevertheless, our study does not suggest a causal link between atypical antipsychotics and the onset of these neurological symptoms, as they were equally frequent among the group of patients who did not receive antipsychotic treatment.